5-Phosphoribosyl-1-pyrophosphate (PRPP) is a key central metabolite that feeds several crucial biosynthetic pathways; these pathways in turn provide the precursors for the synthesis of nucleic acids. These pathways (and respective enzymes) are: 1) pyrimidine nucleotide biosynthesis de novo (orotate PRTase (phosphoribosyltransferase)), 2) purine nucleotide biosynthesis de novo (glutamine:amido PRTase), and 3) purine base "salvage" (adenine PRTase and hypoxanthine-guanine PRTase); a related case is the biosynthesis of NAD+ (nicotinate PRTase). PRPP itself is, of course, the product of PRPP synthetase. I propose to synthesize a completely novel family of non-hydrolyzable, non-metabolizable, isosteric phosphonate PRPP analogs, in which the C(1), or anomeric, -0- is replaced by a -CH2-group. The synthetic route is based on C-glycoside chemistry using a modified Wittig reaction. These resultant compounds will have these (abbreviated) structures: PRCPOP, PRCPCP, PCRCPOP, and PCRCPCP. Each of these compounds will be tested for its effects on the activities and overall mechanisms of the mammalian (many of human origin) enzymes. En route to the PRPP analogs I shall also, by consequence, produce the homologous C(1)- methylenephosphonate analogs of ribose-1-phosphate (R-1-P): the Alpha and Beta "anomers" of R-1-CP. I will then determine the effects of these novel substrate analogs on the following mammalian (some human) activities, which are also important in nucleotide biosynthesis and turnover: purine (hypoxanthine and guanine) nucleoside phosphorylase, and uridine phosphorylase. In addition I will reexamine the properties of the largely-uncharacterized mammalian phosphoribomutase, which catalyzes the conversion of R-5-P to R-1-P thereby competing with PRPP synthetase. The effects of Alpha and Beta R-1-CP and the PRPP analogs on this enzyme will be studied. The large variety of isosteric analogs and target enzymes, as well ast he metabolically critical nature of those targets, provides the potential of identifying some novel and interesting enzyme:antimetabolite pairs for further study. In addition to providing useful information about the mechanisms of (phospho)ribosyl group transfer, such antimetabolites might well offer potential for an untested approach toward development of a novel cancer chemotherapeutic agent.